Thursday, March 30, 2006

The trials (and tribulations) of drug trials

While two of the participants in the disastrous drug trial that came close to killing six volunteers have now returned home, four remain in hospital, one still in a critical condition. The near-fatal consequences of these recent trials have sparked calls for a radical overhaul of drug trials and the safety procedures involved in human testing. It also raises questions about the risks and benefits of clinical trial participation, and places the spotlight on informed consent.

Professor George Zimmer, a cancer patient who participated in a number of Phase I clinical trials, provided an interesting perspective on drug trial participation:
“Human participants in a protocol differ in two ways from the rats and dogs that preceded them. First, because human participants are not distinguished by breed, they do not have identical or blanket reactions to an experiment…Second, human patients have differing mental and personality characteristics…but the trials cannot compensate for the thoughts and emotions of individual participants. These important facets of the whole person are largely ignored when trial programs are designed” (Daugherty, Siegler, Ratain & Zimmer, 1997, p.892).

“Although Professor Zimmer describes personal experiences encountered during his battle against cancer, his views on how some patients respond to incurable illnesses certainly apply to many other terminal diseases. Zimmer raises serious questions about basic aspects of clinical trials…” (Daugherty, Siegler, Ratain & Zimmer, 1997, p.893).

His essay also highlights the importance of considering the unique particularities that each individual trial participant brings to the trial site. In HIV vaccine trials, for instance, there are unique social consequences of HIV infection that must be considered in the ethical analysis of vaccine trials. “People infected with HIV have experienced stigma, marginalization, and discrimination in many forms. Volunteers participating in HIV vaccine trials may be falsely identified as HIV-positive simply through their association with the trial…Thus, the risk of social and psychological harm for human subjects participating in vaccine research is substantial” (Guenter, Esparza & Macklin, 2000, p.38). And this coupled with the physical risks of participating in drug trial research – risks that have been clearly demonstrated in what appeared to be a test for a simple anti-inflammatory drug.

The ethical complexities involved in clinical human subjects research may be one of the factors that have slow down progression to the final step of randomized, controlled large-scale Phase III efficacy trials, despite the fact that many candidate HIV vaccines have proceeded to the point of testing for safety in human subjects (Phase I and Phase II clinical trials). Other challenges facing these trials are scientific, logistical, political, and economic (Guenter, Esparza & Macklin, 2000).

Meanwhile, few drug trials in South Africa seem to get past Phase I research. Could these challenges be part of what is slowing the trial process down? Or is the red tape of regulatory procedures compromising the medical research industry in this country? Clinical trials are pulling in up to R2-billion a year in South Africa, according to a recent report, but researchers fear the industry may be compromised by the slowness of regulatory authorities to approve, or reject, potential trials.

It is not unknown for multinational drugs companies to test unproven drugs on vulnerable subjects in the developing world. Because of this, South African regulators have to balance competing in a competitive international market with ensuring that trials participants are not exploited. But researchers are concerned that lack of human resources is slowing down the clinical trials registration process, encouraging companies to look elsewhere.

Daugherty, C.K., Siegler, M., Ratain, M.J., & Zimmer, G. (1997). Learning from our patients: One participant’s impact on clinical trial research and informed consent. Annals of Internal Medicine, 126, 892-897.

Guenter, D., Esparza, J., & Macklin, R. (2000). Ethical considerations in international HIV vaccine trials: Summary of a consultative process conducted by the Joint United Nations Programme on HIV/AIDS (UNAIDS). Journal of Medical Ethics, 26, 37-43.


Karama said...

Speaking of drug trials, Schering-Plough has one that specifically forbids the participation of African-Americans, for no good reason as far as I can tell.

Debra Leigh Marais said...

Very interesting - I would be interested to know how they reply.